The human SWI/SNF subunit Brm is a regulator of alternative splicing
The human SWI/SNF subunit Brm is a regulator of alternative splicing
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DOI：
10.1038/nsmb1030
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发表时间：
2006-01-01
影响因子：
16.8
通讯作者：
Muchardt, C
中科院分区：
文献类型：
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作者：
Batsché, E;Yaniv, M;Muchardt, C
SWI/SNF（mating-type switch/sucrose nonfermenting）复合物参与启动子上的染色质重塑，在基因的编码区也被检测到。在这里，我们表明，SWI/SNF可以作为一个调节器的选择性剪接。我们发现，催化亚基Brm有利于包括在mRNA的几个基因，包括E-钙粘蛋白，BIM，细胞周期蛋白D1和CD 44的变体外显子。与此相一致，Brm与剪接体的几个组分和Sam 68相关联，Sam 68是一种ERK激活的变体外显子包含增强子。检查的CD 44基因显示，溴诱导积累的RNA聚合酶II（RNAPII）与修改CTD磷酸化模式的区域编码的变体外显子。总而言之，我们的数据表明，在SWI/SNF调控的基因上，Brm通过降低RNAPII延伸率和促进剪接机制向具有次优剪接位点的变体外显子的募集来促进转录和RNA加工之间的串扰。
The SWI/SNF (mating-type switch/sucrose nonfermenting) complex involved in chromatin remodeling on promoters has also been detected on the coding region of genes. Here we show that SWI/SNF can function as a regulator of alternative splicing. We found that the catalytic subunit Brm favors inclusion of variant exons in the mRNA of several genes, including E-cadherin, BIM, cyclin D1 and CD44. Consistent with this, Brm associates with several components of the spliceosome and with Sam68, an ERK-activated enhancer of variant exon inclusion. Examination of the CD44 gene revealed that Brm induced accumulation of RNA polymerase II (RNAPII) with a modified CTD phosphorylation pattern on regions encoding variant exons. Altogether, our data suggest that on genes regulated by SWI/SNF, Brm contributes to the crosstalk between transcription and RNA processing by decreasing RNAPII elongation rate and facilitating recruitment of the splicing machinery to variant exons with suboptimal splice sites.